tbuckley/cabot-search huggingface dataset:
Abstract 15254: <i>Acta2</i> Missense Variant Increases Atherosclerotic Plaque Burdern by Heat Shock Factor 1-Driven Augmented Phenotypic Modulation of Smooth Muscle Cells
Authors: Kaveeta Kaw, Abhijnan Chattopadhyay, Pujun Guan, Jiyuan Chen, Suravi Majumder, Xue Yan Duan, Shuangtao Ma, Chen Zhang, Callie Kwartler, Dianna M Milewicz
Journal: Circulation (2022)

ACTA2 encodes the contractile protein smooth muscle α-actin expressed in smooth muscle cells (SMCs). A heterozygous pathogenic variant in ACTA2 , p.R149C, predisposes to premature coronary artery disease (CAD) in the absence of risk factors. Recent studies have determined that SMCs contribute to atherosclerotic plaque formation after undergoing phenotypic modulation, characterized by de-differentiation and increased expression of macrophage, fibroblast, stem, and osteogenic markers. This SMC modulation is driven in part by exogenous cholesterol entering the endoplasmic reticulum (ER) and activating ER stress, specifically PERK signaling. To determine how a mutation in SM α-actin predisposes to atherosclerosis, Acta2 R149C/+ mice were crossed into Apoe -/- mice and fed a high fat diet for 3 months. Despite no differences in serum lipid levels, the Acta2 R149C/+ Apoe -/- mice have a 3-fold increased plaque burden compared to Apoe -/- mice. SMCs explanted from Acta2 R149C/+ mice have phenotypic modulation at baseline while WT SMCs do not. We determined that misfolding of the R149C SMα-actin activates heat shock factor 1 (HSF1), which increases endogenous cholesterol biosynthesis through increasing HMG-CoA reductase expression. The increase in endogenous cholesterol levels induces ER stress, activates PERK, and augments both modulation of SMCs and atherosclerotic plaque formation. ScRNA sequencing confirms increased HSF1 and PERK signaling and modulation in SMCs in the mutant mice. Importantly, pravastatin treatment dramatically lowers plaque burden to similar low levels of plaque burden in both the Acta2 R149C/+ Apoe -/- and Apoe -/- mice (Fig. 1a) . These studies identify a novel mechanism by which mutant SM α-actin increases endogenous cholesterol biosynthesis and drives atherosclerotic plaque formation, a mechanism that also informs as to why statins are effective in individuals at risk for CAD who do not have elevated plasma cholesterol levels (Fig. 1b) .
Abstract 14899: Ten Year Performance of Convergent Cryoballoon Hybrid Ablation With Left Atrial Appendage Exclusion in Persistent and Long Standing Persistent Atrial Fibrillation: A Trac-Af Registry Outcome Study
Authors: Franccesca Pickmans, Spencer Sherman, Andrew Sherman, Kevin J Makati
Journal: Circulation (2022)

Introduction: Catheter ablation (CA) efficacy in persistent and long standing persistent atrial fibrillation (AF) remains poor. The Convergent procedure with endocardial cryoballoon and left atrial appendage exclusion (LAAE) addresses multiple epicardial/endocardial targets offering a comprehensive approach. We report clinical outcomes in a prospectively collected registry supplemented by continuous device monitoring in a diseased AF patient population. Methods: Single center patient data were retrospectively analyzed in the TRAC-AF registry (NCT05111015) between November 2011-November 2021. Epicardial ablations were performed by cardiothoracic surgeon and endocardial CA performed by electrophysiologist. Clinical follow up was performed at 3, 6, and 12 months and every 6 months thereafter. AF burden was determined from patients with ≥30 days of 24 hr continuous rhythm monitoring following a 90 day blanking period. Results: A total of 228 patients (69% male) received hybrid Convergent ablation. Mean age was 66 yrs, mean BMI was 30.2 ± 6.2, and in 70% of patients, CHA2DS2-VASc was ≥2. Baseline AF types were paroxysmal (7%), persistent (43%), and longstanding persistent (50%). Mean AF duration was 5.1 ± 6.2 yrs. Fifty-seven percent of patients had failed CA prior to hybrid ablation and 30.6% had LAAE with an epicardial clip. Of 228 patients, 114 (50%) had continuous rhythm monitoring. Mean residual AF burden was 5.2 ± 16.3% and of those, 77% had ≤1% mean residual AF burden, and 88% had ≤5% mean residual AF burden. A repeat CA after hybrid Convergent occurred in 23% (53/228) of patients at a mean 645.8 ± 511.4 days from the index procedure with 4.4% requiring &gt;1; 88.5% of all repeat ablations included a mitral annular line. Conclusions: The hybrid Convergent ablation with endocardial cryoballoon and LAAE provides long term sustainable low AF burden despite rigorous endpoint surveillance in a significantly diseased AF population which includes prior failed CA patients over a decade of follow up.
Abstract 14511: A Single Center Experience With the Safety and Feasibility of Concomitant Atrial Fibrillation Ablation and Left Atrial Appendage Occlusion: Six-Month Outcomes
Authors: Ashraf Alzahrani, Rehan Karmali, Felix Berglund, Himanshu Sajja, Benjamin Klein, Alveena Syed, Eoin Donnellan, Oussama M Wazni, Tyler Taigen, Mohamed H Kanj
Journal: Circulation (2022)

Introduction: Given the procedural similarities between atrial fibrillation (AF) catheter ablation and left atrial appendage (LAA) occlusion, interest has grown over recent years in combining them into a single concomitant procedure as a strategy for rhythm control and stroke prevention. We report on the short-term outcomes of the combined procedure in a single center case series. Methods and Results Data was gathered by retrospective chart review. Between June 2015 to August 2021, 242 patients (61% male, mean age 72 ± 8, CHA2DS2-VASc 3.8 ± 1.3, HAS-BLED 2.5 ± 1.1) underwent concomitant AF ablation and LAA occlusion with the Watchman device. Successful occlusion occurred in 224 patients (93%) with a mean procedural time of 182 ± 76 minutes, mean maximum compression of 25 ± 5.5%, and a median number of 1 device. Reasons for aborting included anatomic difficulties (83%), the presence of sludge or thrombus in the LAA (11%), and edema at the site of ablation in only 1 case (6%). Peri-procedural complications included 2 cases of left atrial appendage perforation requiring surgical device extraction, 1 stroke, 6 cases of pericarditis, and 4 vascular access site complications including 1 retroperitoneal bleed, 1 superficial hematoma, 1 persistent bleeding requiring admission, and 1 arteriovenous fistula. 205 patients (92%) had appropriate follow-up within 6 months. Anticoagulation was successfully discontinued in 90 patients (44%) at 3 months, and 178 patients (87%) at 6 months. Antiarrhythmics were discontinued in 25 patients at 3 months (12%) and 35 patients at 6 months (17%). Ninety-day complications included 12 cases of gastrointestinal bleeding, 4 cases of genitourinary bleeding, 3 cases of volume overload, 2 cases of epistaxis, and 1 intracerebral hemorrhage. All patients with repeat imaging (95%) over a mean follow-up duration of 93 days remained with adequate occlusion, with 5 cases of device thrombosis (2%). Conclusion In conclusion, the combined procedures of catheter ablation for AF and LAA occlusion with the Watchman device appears to be safe and feasible. Further data are needed on long-term outcomes of arrhythmia recurrence, bleeding, and thromboembolic events to determine which patients might benefit most from the hybrid approach.
Abstract 14532: Myocardial Blood Flow in Patients Recovered From COVID-19 Infection Using Stress Cardiac Magnetic Resonance
Authors: Shuo Wang, Ilya Karagodin, Haonan Wang, Amita Singh, Joseph Gutbrod, Luis Landeras, Hena Patel, Nazia Alvi, Maxine Tang, Mitchel Benovoy, Martin A Janich, Holly J. Benjamin, Jonathan H. Chung, Amit Patel
Journal: Circulation (2022)

Introduction: Severe COVID-19 infection is known to alter myocardial perfusion through its effects on the endothelium and microvasculature. However, a significant proportion of the world population suffered from only mild COVID-19 symptoms, and it is unknown if their myocardial perfusion is altered following their recovery. Hypothesis: In this study, we aimed to determine if there are detectable abnormalities to myocardial perfusion using cardiac magnetic resonance (CMR) in individuals who have recovered from mild COVID-19 infection. Methods: We conducted a prospective, comparative study of individuals who have recovered from COVID-19 infection (n=33) and risk-factor matched controls (n=27) using regadenoson stress CMR by a 1.5T MR scanner (GE Signa Artist) (figure). Quantitative stress perfusion images were acquired using the dual sequence technique. MBF was measured during rest (rMBF) and stress (sMBF) using Cvi42 software(figure). Myocardial perfusion reserve (MPR) was calculated as sMBF/rMBF. Unpaired t test or the Mann-Whitney U test was used to test differences between the two groups. Results: The median time interval between COVID-19 infection and CMR was 6 (4, 9) months. 31/33 (94%) patients in COVID-19 infection were not hospitalized. Symptoms including chest pain, shortness of breath, syncope, and palpitations were greater in COVID-19 group than in the matched controls (19/33 (58%) vs 2/27 (7%), p&lt;0.001). No differences in rMBF (1.50 ± 0.47 vs 1.36 ± 0.45ml/g/min, p=0.21), sMBF (2.84 ± 0.56 vs 2.75 ± 0.64ml/g/min, p=0.56), or MPR (1.94 (1.48-2.75) vs 2.0 (1.59-3.05), p=0.34) were observed between the groups(figure). Conclusions: No significant abnormalities in myocardial perfusion during rest or stress conditions were seen in individuals who had recovered from mild COVID-19 infection suggesting that microvascular dysfunction is unlikely to be a common sequela in this patient population.
Abstract 14616: Lineage-Specific Integrin alpha-V Augmentation Promotes Integrin/Akt/mTORC1 Signaling Pathway in Marfan Syndrome Aortic Aneurysm
Authors: Ken Nakamura, Nobu Yokoyama, Alex R Dalal, Albert J Pedroza, Matthew Leipzig, Olivia Mitchel, Sho Kusadokoro, Tetsuro Uchida, Michael P Fischbein
Journal: Circulation (2022)

Introduction: Marfan syndrome (MFS) patients classically develop focal aortic root aneurysms. Previously, we demonstrated in vitro activation of the integrin/Akt/mTORC1 signaling pathway in MFS second heart field iPSC derived SMCs. Integrin αV (ITGAV) antagonism via selective inhibitor GLPG0187 attenuated the signaling cascade. Therefore, we hypothesize that ITGAV blockade may have a potential therapeutic effect to reduce MFS aneurysmal growth. Methods: Fbn1 C1039G/+ mice were treated with (1) ITGAV antagonism (GLPG0187, 100mg/kg/day, IP) or (2) vehicle control (age 6-14 weeks). WB and ELISA were performed at baseline and after treatment. Aneurysm growth and elastin fragmentation were measured with ultrasound and histology respectively. Proliferation marker Ki-67 was used with IHC staining. Results: ITGAV and p-Akt protein levels were elevated in Fbn1 C1039G/+ aortic specimens at both 6 and 14 weeks of age compared to wild-type littermate controls. P-Akt and mTORC1 activities were attenuated following GLPG treatment compared to vehicle control (p-Akt Thr308 : 1.37- vs. 1.11-fold, p&lt;0.05; p-RPS6 Ser235/236 : 5.13- vs. 1.15-fold, p&lt;0.001; p-RPS6 Ser240/244 : 4.36- vs. 1.25-fold, p&lt;0.05, n=6). Compared to vehicle control, GLPG reduced aneurysm growth (2.12±0.14mm vs. 1.82±0.19mm, p&lt;0.001, n=12) and elastin fragmentation (1.09 [0.99-1.18] vs. 0.84 [0.75-1.01] breaks/lamina, p&lt;0.05, n=6) in Fbn1 C1039G/+ mice. Ki-67 expression was suppressed with GLPG treatment. Conclusions: As biological proof of concept, GLPG0187 treatment in Fbn1 C1039G/+ mice decreased aneurysm growth via reduced ITGAV signaling. Mechanistically, blockade of ITGAV leads to diminished Akt and mTORC1 activation. Ultimately reducing aortic SMC proliferation, migration and phenotype modulation, which have all been associated with aortic aneurysm development and growth. ITGAV blockade via GLPG0187 may be a promising therapeutic approach to slow MFS aneurysmal growth.
Abstract 14677: Therapeutic Outcomes in Concomitant Cardiogenic Shock and Severe Aortic Stenosis: Insights From the National Inpatient Sample
Authors: Ian Ergui, Michael Dangl, Bertrand Ebner, Rafael J Hernandez, Karla Inestroza, michael Albosta, Carlos Vergara-Sanchez, Jelani Grant, Louis T Vincent, Jennifer Maning, Rosario Colombo
Journal: Circulation (2022)

Introduction: Cardiogenic shock (CS) in patients with concomitant severe aortic stenosis (AS) is a critical combination of pathologies that has been associated with a 43% to 77% in-hospital mortality. There is scant data regarding outcomes after medical management (MM), transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in this high risk population. Methods: The National Inpatient Sample was queried from 2011-2019 for relevant ICD-9 and ICD-10 codes to identify patients with AS and CS who underwent MM, TAVR or SAVR. Binary logistic regression was used to adjust outcomes for significantly different baseline characteristics. Results: We identified a weighted sample of 4,663,000 patients with AS, of which 26,101 had a concurrent diagnosis of CS and did not meet exclusion criteria. Medical management was associated with increased mortality compared to treatment with TAVR or SAVR (aOR 2.231, 95% CI 2.032-2.448, p&lt;0.001). SAVR was associated with decreased mortality when compared to TAVR, although the difference was not statistically significant. Patients that underwent intervention, and specifically SAVR, had lower odds of cardiac arrest than patients that underwent medical management (SAVR aOR 0.514, 95% CI 0.386- 0.685, p&lt;0.001, TAVR aOR 1.946, 95% CI 1.461-2.592, p&lt;0.001). Medical management was associated with decreased risk of complete heart block (aOR 0.402, 95% CI 0.341-0.473, p&lt;0.001), length of stay (8.4±9.9 days versus 9.6±8.5 for TAVR and 11.4±9.7 for SAVR, p&lt;0.001) and cost of stay ($151,605±200,268 versus $352,936 ±297,495 for TAVR and $325,485 ±281,422 for SAVR, p&lt;0.001). Conclusions: Patients with concomitant CS and severe AS have increased mortality with MM as compared to patients that undergo TAVR or SAVR, however there is no significant difference between TAVR and SAVR mortality despite SAVR patients generally having a lower incidence of comorbidities. These patients may benefit from AVR as opposed to MM.
Abstract 14487: Evaluation of Phenotype and Interaction of Endothelial Function at Different Arterial Levels by Simultaneous Measurement of Flow-Mediated Dilation and Endo-PAT; FMD-J B Study
Authors: Nobuyuki Masaki, Bonpei Takase, Takeshi K Adachi
Journal: Circulation (2022)

Introduction: Two representative tests of endothelial function, flow-mediated dilation (FMD) and reactive hypermia index (RHI), often give contradictory results. Hypothesis: Simaltaneous evaluation of the interactions and discordances between two tests of endothelial function for different site might clarify the reasons for the contradictory results. Methods: A total of 966 patients were enrolled in this study. Simultaneous measurement of FMD and RHI by forearm cuff occlusion was repeated every 1.5 years during a 4.5-year observation period. Test results were divided by 4% of FMD and 1.67% of RHI, and the patients were classified into 4 groups. Lifestyle and blood laboratory values were also assessed at each examination. Data were analyzed on both a test-based and patient-based basis. Results: In a total of 1434 tests, there was little relationship between FMD and RHI. Blood glucose levels were negatively correlated with increased brachial artery blood flow velocity after cuff occlusion release (r = 0.095, p &lt; 0.001). Increased blood flow velocity correlated with RHI (r = 0.144, p &lt; 0.001), suggesting that there is an interrelationship between upstream and peripheral blood flow and that hyperglycemia worsens these flows. In addition, delayed time to peak diastole was associated with lower RHI (r=-0.111, p&lt;0.001). Patient-based analysis showed that age, low-density lipoprotein cholesterol, and high-sensitivity CRP were highest in the low FMD/low RHI group, and fasting blood glucose was lowest in the high FMD/RHI group. Antihypertensive medication use, alcohol consumption, and smoking were highest in the low FMD/PAT group. Conclusion: The composite assessment by FMD and RHI is useful to indicate the pathological phenotype of endothelial dysfunction. The group with both low FMD and low RHI were found to be at higher risk. In addition, some FMD components were associated with RHI rather than FMD. A subgroup of patients with benign FMD, but with deteriorated RHI, had a longer time to reach maximal dilation. This possibility should be noted when assessing cardiovascular risk based solely on FMD.
Abstract 15804: Gender-Specific Analysis of Current Trends in Primary Prevention of ASCVD
Authors: Haven Nisly, Ryan Moran
Journal: Circulation (2022)

Introduction: Cardiovascular disease is the leading cause of death in the U.S. for both men and women. Disparities exist not only in women’s outcomes from atherosclerotic cardiovascular disease (ASCVD) but also in assessment of their risk of disease development. This can be attributed in part to the historical misperception that ASCVD affects males at a greater rate than females. This study examines whether female patients are appropriately prescribed statin medication for primary prevention of ASCVD at the same rates as male patients of equivalent risk. Methods: Data were gathered from 11,871 de-identified UC San Diego patient medical records, which included primary care patients ages 40 to 75 without prior ASCVD. The ACC/AHA 10-Year ASCVD Risk Estimator was used to calculate risk scores. The groups of elevated-risk patients, defined by a score greater than or equal to 7.5, of each gender who were and were not prescribed statins were compared using a Chi-Square analysis, conducted in SPSS, in order to determine whether a significant difference existed in appropriate statin prescription between male and female patients. Significance was assessed using the Pearson Chi-Square value compared to a 0.05 significance threshold. Results: In the group of male patients, 796 were on a statin when indicated, compared to the expected value of 803.1, and 807 were not, compared to 789.9 expected. For the female group, 305 patients were on a statin when indicated, compared to 287.9 expected, and 266 were not, compared to 283.1 expected. The Pearson Chi-Square value comparing the groups was 0.095, which is greater than the 0.05 significance threshold. Conclusions: Because of evidence that physicians may be influenced by biases about women’s heart disease risk, this study assessed the hypothesis that there would be a significant difference in appropriate prescription of statins for primary ASCVD prevention between male and female patients. This analysis did not show evidence of a statistically significant difference between the rates of untreated elevated-risk men versus women in this patient population. Though a single-institution study, these findings may signal increasing awareness of women's heart disease risk among primary care physicians.
Abstract 14452: Do Patient-Reported Symptoms on Ambulatory Electrocardiogram Correlate With Atrial Arrhythmia Episodes?
Authors: Zameer Abedin, Maranda Herner, Michael Torre, yue Zhang, Cody Orton, Ann Lyons, Ryan Butcher, Benjamin A Steinberg
Journal: Circulation (2022)

Introduction: Guidelines regarding rhythm control for atrial arrhythmias (AT/AF) are primarily based on symptom burden. Ambulatory electrocardiogram (AECG) monitoring is often performed to evaluate AT/AF burden and guide clinical decision-making. Yet, to date, little is known about the correlation of symptoms reported during AECG with recorded AT/AF. Methods: University of Utah patient AECGs with at least one AT/AF event over 7 or more days of monitoring were retrospectively reviewed - only events with symptoms or with AT/AF were included (other arrhythmias were rare and excluded). Patient triggered symptoms included reported shortness of breath, tiredness, palpitations, dizziness, or passing out. Tetrachoric correlation analysis was performed to evaluate the correlation between symptoms and AT/AF episodes. Results: We identified 742 patients with a mean age of 64 years, 50% female, 22% with chronic heart failure, overall mean CHA 2 DS 2 -VASc score of 2.5 and 67% with scores ≥2. There were 6,289 symptomatic events and 6,900 AT/AF episodes. Among these were 1,025 (16%) episodes of shortness of breath, 854 (14%) of tiredness, 2,660 (42%) of palpitations, 794 (13%) of dizziness, and 95 (2%) of passing out. Symptomatic events were less likely to predict simultaneous AT/AF compared to sinus rhythm on AECG, with a moderate inverse tetrachoric correlation of -0.66 (range -1 to 1, with 1 representing perfect positive correlation). Conclusion: Patient-triggered symptomatic events were inversely correlated with recorded AT/AF events and represented an unacceptable marker of actual arrhythmia. A more holistic approach to assessment of ATAF symptoms is needed to improve patient selection for rhythm control therapy.
Abstract 158: Adult Defibrillation Shocks Do Not Cause Cardiac Damage In A Pediatric Porcine Model
Authors: Ben McCartney, Adam Harvey, Amy Kernaghan, Paul Crawford, Raymond Bond, Dewar Finlay, David McEneaney
Journal: Circulation (2022)

Introduction: AEDs often utilize specific modes for treating pediatric patients, enabling reduced energy defibrillation and pediatric specific guidance on performing CPR. If a pediatric mode is not available, current guidelines recommend use of adult mode. It is not fully understood if delivery of adult mode shocks or CPR results in cardiac damage in children. The aim of this pilot study was to observe the effects of delivering either adult shocks or CPR during sinus rhythm in pediatric weight swine. Methods: Six anesthetized swine (10-12 kg) were studied. Four received three adult unsynchronized shocks (150-150-200 Joules) (HeartSine, UK) without induction of VF to isolate the effect of shocks alone. Two received three, two-minute episodes of CPR. A Philips MRx (Philips, USA) recorded CPR depth. ST-segment deviation was recorded before shocks and at 10-seconds and 60-seconds post-shock. Animals then entered a 4-hour monitoring period were blood samples and echocardiographic images were taken at +2 hours and +4 hours. Results: No shock (0/12) or episode of CPR (0/6) delivered during sinus rhythm resulted in conversion to an arrest rhythm. CPR was delivered at depths between 21 and 39 mm. There was no significant change in ST-segment deviation, cardiac troponin I, creatine phosphokinase or left ventricular ejection fraction from baseline values for either group (Table 1). Additionally, there were no significant differences between the two groups for any endpoint. Conclusions: Neither adult energy shocks nor CPR delivered to pediatric weight pigs resulted in significant adverse effects by any metric analyzed. This suggests that application of adult shock energies and CPR without experimental confounders (e.g. ischemia, metabolic disturbance) does not result in significant myocardial damage in this model of pediatric resuscitation. Future studies should investigate the effect of guideline depth CPR in this model. Note: this is a pilot study with a limited sample size.